Seldomycin Factor 5 is a broad spectrum antibacterial agent elaborated by Streptomyces hofunensis and for which the following formula has been elucidated. ##STR2##
Seldomycin factor 5 is also known as Antibiotic XK-88-5. It is a highly active antibiotic, effective against both Gram-positive and Gram-negative organisms such as Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli and Proteus, Enterobacter and Salmonella species. Seldomycin factor 5 is only one of a number of antibiotics produced by the fermentation of Streptomyces hofunensis. The isolation and characteristics of seldomycin factor 5 is described in U.S. Pat. No. 3,939,043 (1976) and the elucidation of its structure is described in the Journal of Antibiotics 30 pages 39-49 (1977).
The nomenclature of the above formula is simplified by the following numbering system in which the carbons of the cylitol moiety, also known as the 2-deoxystreptamine moiety, are numbered 1 through 6. The carbons of the hexose moiety are numbered with a single prime, 1' through 6' and the carbons of the pentose moiety are numbered with a double prime, 1" through 5". ##STR3##
Microorganisms are known to frequently acquire resistance to aminoglycoside antibiotics by a mechanism known in the art as "R-Factors". Very generally an "R-Factor" is the extrachromosomal genetic capability of biochemically modifying the antibiotics in such as way as to interfere with its antibacterial action, thereby enabling the organism to grow.
The difficulty of selectively acylating or alkylating any one amine of an aminoglycoside increases sharply with increasing numbers of amino groups in the molecule. This increase in difficulty is especially marked if the amino groups are all of the same substitution pattern. Thus selective acylation or alkylation at one of the amines of seldomycin factor 5 which contains six primary amines presents a formidable problem.
Other inventions for solutions to this problem have been described. U.S. Pat. No. 4,002,608 describes a method for the preparation of 1-N-alkyl seldomycin factor 5 via initial formation of 2"-N-alkanoyl substituted seldomycin factor 5. No description with respect to the yield from this method nor of the purity of the products are made nor is the method applicable to acylation at the 1-N-position.